An overreliance on proprioceptive (intrinsic) sensory input from the body, compared to visual (extrinsic) input from the environment, may underpin core features of autism spectrum disorder (ASD). We developed an engaging videogame (“HaptiKart”) as a tool to examine differences in sensory-motor bias (proprioceptive vs. visual) in children and adults with ASD and whether bias correlates with age, core autism features, and intellectual ability. Eighty-one participants (33 ASD, 48 typically-developing, TD) aged 8–31 years played “HaptiKart,” a driving videogame with a force-feedback steering wheel that provided “steering assist” during gameplay. In separate trials, proprioceptive and visual feedback were selectively delayed, and differences in driving error between the conditions were used to calculate perceptual bias scores. Effects of autism diagnosis and age on bias scores were examined, controlling for sex, as were associations of perceptual bias with autism symptom severity (ADOS-2, SRS-2), attention-deficit symptom severity (Conners4 ADHD Total Scores) ratings, and IQ (general ability index, GAI). The ASD group exhibited significantly higher proprioceptive bias than did the TD group (p = 0.002). There was a trend for decreasing proprioceptive bias with age, but no significant diagnosis-by-age interaction. Increased proprioceptive bias correlated with higher autism severity and with lower IQ, but not ADHD symptoms. HaptiKart provides a highly scalable approach for measuring sensory-motor bias, revealing that individuals with ASD show elevated proprioceptive bias, correlating with autism severity. HaptiKart’s sensory-motor bias measure may thereby serve as a digital biomarker for addressing autism heterogeneity in ways that can improve targeted intervention.

Atypical motor function is a highly prevalent clinical feature of autism spectrum disorder (ASD). Differences in motor function both persist across the lifespan and scale linearly with the magnitude of core ASD symptom presentation. Because motor differences may be apparent earlier than core autism features, objective, quantifiable measures of motor function may help clinicians with early detection of neurodevelopmental delays/deviance, early diagnosis of ASD, and later differential diagnosis. Moreover, nuanced motor biomarkers represent a promising approach to parse presumed mechanistic heterogeneity across the autism spectrum, particularly as it relates to guiding precision intervention. To achieve these mechanistic-science and biomarker-development goals, we propose approaches to transcend limitations we see within the corpus of autism motor research as a whole. First, we suggest more transdiagnostic research to establish the specificity of particular motor behaviors for autism (vs. other neurodevelopmental conditions that also show motor atypicalities). Relatedly, enhancing the specificity of both motor constructs and core-symptom constructs (social-communicative, restricted and repetitive behaviors/interests [RRB]) within autism sensory-motor research will be essential for parsing the heterogeneity within the autism spectrum. Finally, in order to sharpen our mechanistic understanding, we recommend experimental designs that simultaneously and competitively test multiple cognitive-motor theories of autism within frameworks of Computational Motor Control and Bayesian Inference, as this approach will aid in developing clinically meaningful objective motor biomarkers based on mechanism. Each of the cognitive-motor theories we discuss in the chapter (hypo-priors, hyper-priors, prediction, inter-sensory bias, and sensory-motor transformation) ascribes different features of autism to different mechanisms; we recognize that different mechanisms may be at play across individuals within the heterogeneous autism spectrum in a way that accounts for both motor and non-motor heterogeneity. Finally, we discuss neuroanatomical correlates that may underpin each theory proposed, providing a brain-behavioral link between the early emerging “lower-level” features of autism (i.e., motor differences and low-order RRBs) and developmentally later emerging higher-level ASD symptomology (i.e., social communication differences and high-level RRBs).

Cerebellar transcranial direct current stimulation (tDCS) enhances motor skill and learning in relatively simple motor tasks, but it is unclear if c-tDCS can improve motor performance in complex motor tasks. The purpose of this study was to determine the influence of c-tDCS applied over multiple days on motor learning in a complex overhand throwing task. In a double-blind, randomized, between-subjects, SHAM-controlled, experimental design, 30 young adults were assigned to either a c-tDCS or a SHAM group. Participants completed three identical experiments on consecutive days that involved overhand throwing in a pre-test block, five practice blocks with concurrent c-tDCS, and a post-test block. Overhand throwing endpoint accuracy was quantified as the endpoint error. The first dorsal interosseous muscle motor evoked potential (MEP) amplitude elicited by transcranial magnetic stimulation was used to quantify primary motor cortex (M1) excitability modulations via c-tDCS. Endpoint error significantly decreased over the 3 days of practice, but the magnitude of decrease was not significantly different between the c-tDCS and SHAM group. Similarly, MEP amplitude slightly increased from the pre-tests to the post-tests, but these increases did not differ between groups. These results indicate that multi-day c-tDCS does not improve motor learning in an overhand throwing task or increase M1 excitability.

The exclusion of high-motion participants can reduce the impact of motion in functional Magnetic Resonance Imaging (fMRI) data. However, the exclusion of high-motion participants may change the distribution of clinically relevant variables in the study sample, and the resulting sample may not be representative of the population. Our goals are two-fold: 1) to document the biases introduced by common motion exclusion practices in functional connectivity research and 2) to introduce a framework to address these biases by treating excluded scans as a missing data problem. We use a study of autism spectrum disorder in children without an intellectual disability to illustrate the problem and the potential solution. We aggregated data from 545 children (8-13 years old) who participated in resting-state fMRI studies at Kennedy Krieger Institute (173 autistic and 372 typically developing) between 2007 and 2020. We found that autistic children were more likely to be excluded than typically developing children, with 28.5% and 16.1% of autistic and typically developing children excluded, respectively, using a lenient criterion and 81.0% and 60.1% with a stricter criterion. The resulting sample of autistic children with usable data tended to be older, have milder social deficits, better motor control, and higher intellectual ability than the original sample. These measures were also related to functional connectivity strength among children with usable data. This suggests that the generalizability of previous studies reporting naïve analyses (i.e., based only on participants with usable data) may be limited by the selection of older children with less severe clinical profiles because these children are better able to remain still during an rs-fMRI scan. We adapt doubly robust targeted minimum loss based estimation with an ensemble of machine learning algorithms to address these data losses and the resulting biases. The proposed approach selects more edges that differ in functional connectivity between autistic and typically developing children than the naïve approach, supporting this as a promising solution to improve the study of heterogeneous populations in which motion is common.

Background A significant challenge that non-elite collegiate triathletes encounter during competition is the decline in running performance immediately after cycling. Therefore, the purpose of this study was to determine if performing a 40-km bout of cycling immediately before running would negatively influence running economy and mechanical efficiency of running during simulated race conditions in collegiate triathletes. Methods Eight competitive club-level collegiate triathletes randomly performed two trials: cycling for 40 km (Cycle-Run) or running for 5 km (Run–Run), immediately followed by a four-minute running economy and mechanical efficiency of running test at race pace on an instrumented treadmill. Blood lactate, respiratory exchange ratio, mechanical work, energy expenditure, and muscle glycogen were also measured during the four-minute running test. Results Mechanical efficiency of running, but not running economy, was significantly lower in Cycle-Run, compared to Run–Run (42.1 ± 2.5% vs. 48.1 ± 2.5%, respectively; p = 0.027). Anaerobic energy expenditure was significantly higher in the Cycle-Run trial, compared to the Run–Run trial (16.3 ± 2.4 vs. 7.6 ± 1.1 kJ; p = 0.004); while net (151.0 ± 12.3 vs. 136.6 ± 9.6 kJ; p = 0.204) and aerobic energy expenditure (134.7 ± 12.3 vs. 129.1 ± 10.5 kJ; p = 0.549) were not statistically different between trials. Analysis of blood lactate, respiratory exchange ratio, mechanical work, and changes in muscle glycogen revealed no statistically significant differences between trials. Conclusions These results suggest that mechanical efficiency of running, but not running economy, is decreased and anaerobic energy expenditure is increased when a 40-km bout of cycling is performed immediately before running in collegiate triathletes.

We measured cortical activity during gross motor imitation and observation with HD-DOT. Data were not contaminated by motion and results indicate differential neural responses in multiple cortical areas during imitation compared to observation.

Background: Classic psychedelics, such as psilocybin and LSD, and other serotonin 2A receptor (5-HT2AR) agonists evoke acute alterations in perception and cognition. Altered thalamocortical connectivity has been hypothesized to underlie these effects, which is supported by some functional MRI (fMRI) studies. These studies have treated the thalamus as a unitary structure, despite known differential 5-HT2AR expression and functional specificity of different intrathalamic nuclei. Independent Component Analysis (ICA) has been previously used to identify reliable group-level functional subdivisions of the thalamus from resting-state fMRI (rsfMRI) data. We build on these efforts with a novel data-maximizing ICA-based approach to examine psilocybin-induced changes in intrathalamic functional organization and thalamocortical connectivity in individual participants. Methods: Baseline rsfMRI data (n=38) from healthy individuals with a long-term meditation practice was utilized to generate a statistical template of thalamic functional subdivisions. This template was then applied in a novel ICA-based analysis of the acute effects of psilocybin on intra- and extra-thalamic functional organization and connectivity in follow-up scans from a subset of the same individuals (n=18). We examined correlations with subjective reports of drug effect and compared with a previously reported analytic approach (treating the thalamus as a single functional unit). Results: Several intrathalamic components showed significant psilocybin-induced alterations in spatial organization, with effects of psilocybin largely localized to the mediodorsal and pulvinar nuclei. The magnitude of changes in individual participants correlated with reported subjective effects. These components demonstrated predominant decreases in thalamocortical connectivity, largely with visual and default mode networks. Analysis in which the thalamus is treated as a singular unitary structure showed an overall numerical increase in thalamocortical connectivity, consistent with previous literature using this approach, but this increase did not reach statistical significance. Conclusions: We utilized a novel analytic approach to discover psilocybin-induced changes in intra- and extra-thalamic functional organization and connectivity of intrathalamic nuclei and cortical networks known to express the 5-HT2AR. These changes were not observed using whole-thalamus analyses, suggesting that psilocybin may cause widespread but modest increases in thalamocortical connectivity that are offset by strong focal decreases in functionally relevant intrathalamic nuclei.

This study examined whether disruptions in connectivity involving regions critical for learning, planning, and executing movements are relevant to core autism symptoms. Spatially constrained ICA was performed using resting-state fMRI from 419 children (autism spectrum disorder (ASD) = 105; typically developing (TD) = 314) to identify functional motor subdivisions. Comparing the spatial organization of each subdivision between groups, we found voxels that contributed significantly less to the right posterior cerebellar component in children with ASD versus TD (P <0.001). Next, we examined the effect of diagnosis on right posterior cerebellar connectivity with all other motor subdivisions. The model was significant (P = 0.014) revealing that right posterior cerebellar connectivity with bilateral dorsomedial primary motor cortex was, on average, stronger in children with ASD, while right posterior cerebellar connectivity with left-inferior parietal lobule (IPL), bilateral dorsolateral premotor cortex, and supplementary motor area was stronger in TD children (all P ≤0.02). We observed a diagnosis-by-connectivity interaction such that for children with ASD, elevated social-communicative and excessive repetitive-behavior symptom severity were both associated with right posterior cerebellar-left-IPL hypoconnectivity (P ≤0.001). Right posterior cerebellar and left-IPL are strongly implicated in visuomotor processing with dysfunction in this circuit possibly leading to anomalous development of skills, such as motor imitation, that are crucial for effective social-communication. LAY SUMMARY: This study examines whether communication between various brain regions involved in the control of movement are disrupted in children with autism spectrum disorder (ASD). We show communication between the right posterior cerebellum and left IPL, a circuit important for efficient visual-motor integration, is disrupted in children with ASD and associated with the severity of ASD symptoms. These results may explain observations of visual-motor integration impairments in children with ASD that are associated with ASD symptom severity.

Background:Motor imitation difficulties are pervasive in children with Autism Spectrum Disorder (ASD). Previous research demonstrated the validity and reliability of an algorithm called Computerized Assessment of Motor Imitation (CAMI) using 3D depth cameras. However, incorporating CAMI into serious games and making it accessible in clinic and home settings requires a more scalable approach that uses "off-the-shelf" 2D cameras. Method:In a brief (one-minute) task, children (23 ASD, 17 typically developing [TD]) imitated a model's dance movements while simultaneously being recorded using Kinect Xbox motion tracking technology (Kinect 3D) and a single 2D camera. Pose-estimation software (OpenPose 2D) was used on the 2D camera video to fit a skeleton to the imitating child. Motor imitation scores computed from the fully automated OpenPose 2D CAMI method were compared to scores computed from the Kinect 3D CAMI and Human Observation Coding (HOC) methods. Results:Motor imitation scores obtained from the OpenPose 2D CAMI method were significantly correlated with scores obtained from the Kinect 3D CAMI method (r 40 = 0.82, p < 0.001) and the HOC method (r 40 = 0.80, p < 0.001). Both 2D and 3D CAMI methods showed better discriminative ability than the HOC, with the Kinect 3D CAMI method outperforming the OpenPose 2D CAMI method (area under ROC curve (AUC): AUCHOC = 0.799, AUC2D-CAMI = 0.876, AUC3D-CAMI = 0.94). Finally, all motor imitation scores were significantly associated with the social-communication impairment (all p ≤ 0.003). Conclusions:This pilot-study demonstrated that motor imitation can be automatically quantified using a single 2D camera.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a behavioral phenotype characterized by impaired development of social-communicative skills and excessive repetitive and stereotyped behaviors. Despite high phenotypic heterogeneity in ASD, a meaningful subpopulation of children with ASD (∼90%) show significant general motor impairment. More focused studies on the nature of motor impairment in ASD reveal that children with ASD are particularly impaired on tasks such as ball catching and motor imitation that require efficient visual-motor integration (VMI). Motor computational approaches also provide evidence for VMI impairment showing that children with ASD form internal sensorimotor representations that bias proprioceptive over visual feedback. Impaired integration of visual information to form internal representations of others' and the external world may explain observed impairments on VMI tasks and motor imitation of others. Motor imitation is crucial for acquiring both social and motor skills, and impaired imitation skill may contribute to the observed core behavioral phenotype of ASD. The current review examines evidence supporting VMI impairment as a core feature of ASD that may contribute to both impaired motor imitation and social-communicative skill development. We propose that understanding the neurobiological mechanisms underlying VMI impairment in ASD may be key to discovery of therapeutics to address disability in children and adults with ASD.

Mirror overflow is a developmental phenomenon defined as unintentional movements that mimic the execution of intentional movements in homologous muscles on the opposite side of the body. In children with attention-deficit/hyperactivity disorder (ADHD), mirror overflow is commonly excessive, abnormally persistent, and correlated with ADHD symptom severity. As such, it represents a promising clinical biomarker for disinhibited behavior associated with ADHD. Yet, the neural underpinnings of mirror overflow in ADHD remain unclear. Our objective was to test whether intrinsic interhemispheric functional connectivity between homologous regions of the somatomotor network (SMN) is associated with mirror overflow in school age children with and without ADHD using resting state functional magnetic resonance imaging. To this end, we quantified mirror overflow in 119 children (8–12 years old, 62 ADHD) during a finger sequencing task using finger twitch transducers affixed to the index and ring fingers. Group ICA was used to identify right- and left-lateralized SMNs and subject-specific back reconstructed timecourses were correlated to obtain a measure of SMN interhemispheric connectivity. We found that children with ADHD showed increased mirror overflow (p < 0.001; d = 0.671) and interhemispheric SMN functional connectivity (p = 0.023; d = 0.521) as compared to typically developing children. In children with ADHD, but not the typically developing children, there was a significant relationship between interhemispheric SMN functional connectivity and mirror overflow (t = 2.116; p = 0.039). Our findings of stronger interhemispheric functional connectivity between homologous somatomotor regions in children with ADHD is consistent with previous transcranial magnetic stimulation and diffusion-tractography imaging studies suggesting that interhemispheric cortical inhibitory mechanisms may be compromised in children with ADHD. The observed brain-behavior correlation further suggests that abnormally strong interhemispheric SMN connectivity in children with ADHD may diminish their ability to suppress overflow movements.

Bacicground: Postural control deficits are commonly reported in children with Autism Spectrum Disorder (ASD). However, identification of specific postural sway features that differentiate ASD from other neurodevelopmental disorders has not been examined. The current study employs a cross-syndrome approach by comparing postural sway area and direction-specific features of sway magnitude, sway velocity, and sway complexity between children with ASD, Fetal Alcohol Spectrum Disorder (FASD), Attention-Deficit Hyperactivity Disorder (ADHD), and typically developing (TD) controls. Method: Eighty children (7-17 years old) participated in this study. Postural sway was measured on a force plate during 30-s of bilateral quiet stance and balance was assessed using a timed unipedal stance test. Results: Results showed that (1) postural sway area and mediolateral (ML) sway magnitude were significantly greater in children with ASD vs. all groups (p < 0.05); (2) anteroposterior (AP) sway magnitude and velocity were significantly greater in children with ASD vs. TD controls-only (p < 0.05); and (3) static balance was similarly impaired in all clinical groups compared to TD children (p < 0.05). Conclusions: ASD-specific postural sway features were identified using a cross-syndrome design. Identifying ASD-specific motor impairments can be useful to understanding the neurological underpinnings of ASD.

Impairments in visuomotor integration (VMI) may contribute to anomalous development of motor, as well as social‐communicative, skills in children with autism spectrum disorder (ASD). However, it is relatively unknown whether VMI impairments are specific to children with ASD versus children with other neurodevelopmental disorders. As such, this study addressed the hypothesis that children with ASD, but not those in other clinical control groups, would show greater deficits in high‐VMI dynamic grip‐force tracking versus low‐VMI static presentation. Seventy‐nine children, aged 7–17 years, participated: 22 children with ASD, 17 children with fetal alcohol spectrum disorder (FASD), 18 children with Attention‐Deficit Hyperactivity Disorder (ADHD), and 22 typically developing (TD) children. Two grip‐force tracking conditions were examined: (1) a low‐VMI condition (static visual target) and (2) a high‐VMI condition (dynamic visual target). Low‐frequency force oscillations <0.5 Hz during the visuomotor task were also examined. Two‐way ANCOVAs were used to examine group x VMI and group x frequency effects ( α = 0.05). Children with ASD showed a difficulty, above that seen in the ADHD/FASD groups, tracking dynamic, but not static, visual stimuli as compared to TD children. Low‐frequency force oscillations <0.25 Hz were also significantly greater in the ASD versus the TD group. This study is the first to report VMI deficits during dynamic versus static grip‐force tracking and increased proportion of force oscillations <0.25 Hz during visuomotor tracking in the ASD versus TD group. Dynamic VMI impairments may be a core psychophysiologic feature that could contribute to impaired development of motor and social‐communicative skills in ASD. Lay Summary Children with autism spectrum disorder (ASD) show difficulties using dynamic visual stimuli to guide their own movements compared to their typically developing (TD) peers. It is unknown whether children without a diagnosis of ASD, but with other neurological disorders, show similar difficulties processing dynamic visual stimuli. In this study, we showed that children with ASD show a difficulty using dynamic, but not static, visual stimuli to guide movement that may explain atypical development of motor and social skills.

Background: Manual dexterity (MD) is important for performing most activities of daily living, and children with ASD show MD deficits. However, the specificity of MD deficits in children with ASD has not previously been examined. Similar to children with ASD, extant evidence suggests children with Fetal Alcohol Spectrum Disorder (FASD) and Attention-Deficit Hyperactivity Disorder (ADHD) also show MD impairments. The purpose of this study was to examine the specificity MD deficits in children with ASD using a cross-syndrome design. We examined dominant (D) and non-dominant (ND) hand performance using a relatively large sample of children with ASD, FASD, ADHD, and typically developing (TD) children. Method: Seventy-two right-handed children (7-17 years old) participated in this study. To examine MD, the 9-hole pegboard test was completed on the D and ND-hands. The fastest time of three attempts was recorded. HPA was defined as the percent difference between D and ND-hand times. Results: D-hand MD was significantly worse in children with ASD vs. typically developing (TD) children (p = 0.002). ND-hand dexterity was significantly worse in children with ASD vs. FASD (p = 0.049) and TD groups (p = 0.004). Hand performance asymmetry (HPA) was significantly lower in the FASD group compared to both the ASD and ADHD groups (p < 0.05). Conclusions: These results show that children with ASD show specific deficits in MD not observed in children with FASD or ADHD. Furthermore, HPA was found to be a sensitive measure to prenatal alcohol exposure. Neurobiological mechanisms of ASD and FASD are discussed.

Introduction Force platforms and pressure-measuring insoles are the most common tools used for measuring center of pressure. Earlier studies to assess these instruments suffered from limited sample sizes or an inadequate range of participant foot sizes. The purpose of this study was to propose new methods to extract and calculate comparably accurate center of pressure for the Kistler® force platform and Medilogic® insoles. Methods Center of pressure data were collected from 65 participants wearing pressure-measuring insoles (six different sizes). Participants walked over consecutive force platforms for three trials while wearing pressure-measuring insoles within socks. Onset force thresholds and center of pressure segment length thresholds were used to determine accurate center of pressure path length and width. A single step for each foot and trial was extracted from both instruments. Results A strong correlation was observed between instruments in center of pressure length (4.12 ± 6.72% difference, r = 0.74). Center of pressure width varied and was weakly correlated (–7.04 ± 4.48% difference, r = 0.11). Conclusions The results indicate that both instruments can measure center of pressure path length consistently and with comparable accuracy (differences < 10%). There were differences between instruments in measuring center of pressure path width, which were attributed to the limited number of sensors across the width of the insoles.

ABSTRACT Background Motor deficits in children with Autism Spectrum Disorder (ASD) are highly prevalent. High variability of motor output is commonly reported in children with ASD. Visual cueing using an exergame may be an effective intervention to reduce motor variability in children with ASD. Aim To examine the effect of visual cueing on two-legged hopping variability in children with ASD. Methods Four children with ASD and six age-matched TD controls performed three 20-s hopping trials with no visual cueing (no cue = NC) and with a 2 Hz visual cue (visual cue = VC). Three-dimensional kinematic data of the sacrum marker and ground reaction force were collected during each hopping trial. Variability was determined using the intra-trial coefficient of variation (CoV) of hopping frequency, hop height, and negative sacral displacement Results A marginally significant interaction between GROUP (ASD/TD) and CUE type (NC/VC) was observed for hopping frequency variability ( p = 0.06) indicating greater impairment in the ASD group vs. TD group with visual vs. no-cueing. The main effect of group showed a statistically significant difference in hopping frequency ( p = 0.037), hopping frequency variability ( p = 0.008), and negative sacrum displacement variability ( p = 0.04). Conclusion This pilot study confirmed high motor variability in the amplitude and frequency of repetitive movements in children with ASD. However, visual cueing was ineffective at reducing the variability of motor output in children with autism.

•Performance of fixed and a load adaptive-threshold methods to identify active sensors from Medilogic® insoles was examined.•Performance was evaluated by comparing plantar contact area from the insole to a validated optical pedography method.•The adaptive-threshold method performed better than the fixed-threshold method at reducing PA error.•Adaptive-thresholds should be examined using other insole brands to examine the generalizability of this method.

ABSTRACT Weighted vests (WV) are used to influence behavior through sensory integration in children with autism spectrum disorder (ASD). However, WV effects on motor ability during walking are not well understood in this population despite the growing acceptance that motor impairment is a prominent feature of ASD. This study aimed to evaluate the effects of a WV (15% body mass) on spatial–temporal parameters and the control of the center of mass and the hip, knee, and ankle joints in children with ASD during walking using group and single-subject analyses. Eight male children (11 ± 4 yr, 1.45 ± 0.25 m, 55.28 ± 26.20 kg) with ASD walked overground with and without a WV while three-dimensional kinematic data were obtained. A two-way ANOVA and a model statistic technique ( α = 0.05) were used to test for group and single-subject differences, respectively, for stride length, stride time, and smoothness of the center of mass and hip, knee, and ankle joint rotations. At the group level, stride length decreased ( P = 0.018) in response to the WV perturbation, although no other differences were detected for any other variable. At the single-subject level, numerous differences ( P < 0.05) were detected for each variable, although the differences detected were unique to each individual. WV use can alter gross movement function and body control during walking in some children with ASD. We suggest researchers and clinicians interested in evaluating WV use as a therapeutic modality to mitigate motor impairment in children with ASD proceed at the individual level to reveal individual responses to a WV intervention.